CELL INTELLIGENCE · 肿瘤细胞治疗研究

Key Inclusion Criteria:

* Relapsed or refractory T-ALL/T-LBL following at least one (≥18 years old) or two (\<18 years old) standard prior lines of combination cytotoxic therapy
* CCR9-positive disease as assessed by flow cytometry
* T-LBL patients only: Patients must have measurable disease
* Agreement to have a pregnancy test, use adequate contraception (if applicable)
* Written informed consent

Key Exclusion Criteria:

* ECOG performance score \>2 (patients aged ≥10 years old) OR Lanksy score ≤50% (patients aged \<10 years old)
* Stem Cell Transplant patients only: active significant acute GvHD or moderate/severe chronic GvHD requiring immunosuppressive therapy and/or systemic steroids
* Active CNS involvement of disease
* Active hepatitis B, C or HIV infection
* Oxygen saturation ≤90% on air
* Bilirubin \>3 x upper limit of normal
* GFR \<30 ml/min
* Cardiac dysfunction
* Patients receiving corticosteroids at a supraphysiological dose that cannot be discontinued
* Known allergy to any component of the ATIMP
* Any contraindications to lymphodepletion or to the use of cyclophosphamide or fludarabine as per local SmPC
* Women who are pregnant or breastfeeding
* Life expectancy \<3 months
* Fulminant or rapidly progressive disease

主要终点：Feasibility of generation of CARCCR9 T cells as evaluated by the number of therapeutic products generated. · To determine the feasibility of semi-automated autologous CARCCR9 T cells manufacture in patients with r/r T-ALL/T-LBL, in the setting of a Phase I trial. · 2 years；Incidence of treatment-related adverse events (safety and tolerability) · Incidence of grade 3-5 toxicity causally related to the ATIMP. · From CAR T cells infusion until 28 days post infusion
次要终点：Persistence of CARCCR9 T cells；Expansion of CARCCR9 T cells；Potential efficacy of CARCCR9 T cells；Potential efficacy of CARCCR9 T cells；Time to disease progression；Event free survival；Overall survival

• Autologous anti-CCR9 CAR T cells · EXPERIMENTAL · Patients will receive autologous anti-CCR9 CAR T cells intravenously.

The goal of this clinical trial is to learn if anti-CCR9 CAR T cells (which will be made using the patient's own blood cells) are safe and which dose should be used in children and adults with T cell leukaemia and lymphoma. Participants will: * have T cells collected from their blood and these T cells will be used to make the CAR-T cells in a specialized laboratory. * be admitted at the hospital a week before the CAR T cells infusion to receive a short course of chemotherapy drugs which prepare the body to receive the CAR T cells. * be given the CAR T cells into their vein. * stay in the hospital for a minimum of 2 weeks to be closely monitored * following discharge, participants will come to the clinic for check-ups (approximately 12 visits in the first two years) * during screening, treatment and follow up visits, participants will have physical examination, collection of blood samples and bone marrow biopsies and/or imaging tests (CT/PET-CT scans) depending on their type of T-cell cancer.